Patent EA-003667-B1 (EA)
Title: Esters of (+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidinemetahanol and their use as prodrugs of the 5ht2a receptor antagonists mdl 110,907
Inventor: CARR ALBERT A
IPC: A61P9/10
Filed: 1998-10-14
Abstract: 1. A compound of Formula I: wherein R is C4-C20 alkyl, or a stereoisomer or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1 wherein R is a straight chain C4-C20 alkyl. 3. The compound of claim 1 selected from the group comprising: (+)-.alpha.-(2,3-Dimethyoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinementhanol decanoate; (+)-.alpha.-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol hexanoate; (+)-.alpha.-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol octanoate; (+)-.alpha.-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol hexadecanoate; (+)-.alpha.-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol 2,2-dimethyloctanoate. 4. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. 5. The pharmaceutical composition of claim 4 wherein the R is C9 straight chain alkyl and in which the acceptable carrier is a pharmaceutically acceptable oil selected from the group consisting of sesame, olive, arachnis, maize, almond, cottonseed, peanut and castor oil. 6. The pharmaceutical composition of claim 5 wherein the oil is sesame oil. 7. A method for antagonizing the effects of serotonin at the 5HT2a receptor comprising administering a therapeutically effective amount of a compound according to claim 1 to a patient in need thereof. 8. The method of claim 7 wherein R is C9 straight chain alkyl. 9. The method of claim 7 wherein the compound is administered by intramuscular or subcutaneous route. 10. The method of claim 7 wherein the compound is administered by intramuscular route, and the effects of serotonin at the 5HT2a receptor are antagonized from about 2 weeks to about one month. 11. A method of treating a patient suffering from one or more diseases, selected from psychical disorder, schizophrenia, bipolar depression, depression, anxiety, obsessive compulsive disorder, drug addition, coronary vasospasm, angina, and diseases associated with thrombotic illness comprising administering to the patient a therapeutically effective amount of a compound according to claim 1. 12. The method of claim 11 wherein R is C9 straight chain alkyl. 13. The method of claim 11 wherein the compound is administered by intramuscular or subcutaneous route. 14. The method of claim 11 wherein the compound is administered by intramuscular route, and the patient is treated from about 2 weeks to about one month. 15. A method of making a compound of Formula I: wherein R is C4-C20 alkyl, or a stereoisomer or a pharmaceutically acceptable salt thereof; comprising reacting alcohol (5) with an acid halide of the formula RC(O)X, an acid anhydride of the formula (RCO)2O or a carboxylic acid of the formula RCO2H wherein R is as previously defined and X is a chloro or bromo, in the presence of a sufficient amount of an appropriate base to make the compound of Formula I. 16. The method of claim 15 wherein X is chloro and R is straight chain alkyl. 17. The method of claim 15 wherein R is C9 straight chain or branched alkyl, and the base is triethylamine. 18. The method of claim 15 wherein the alcohol (5) is reacted with RCOX wherein R is C9 straight chain alkyl and X is chloro. 19. A compound according to claim 1 for use as a pharmaceutically active substance.